Naturally acquired inhibitory antibodies toPlasmodium vivaxDuffy binding protein are short-lived and allele-specific following a single malaria infection

Abstract

SummaryThe Duffy binding protein of Plasmodium vivax (DBP) is a critical adhesion ligand that participates in merozoite invasion of human Duffy-positive erythrocytes. A small outbreak of P. vivax malaria, in a village located in a non-malarious area of Brazil, offered us an opportunity to investigate the DBP immune responses among individuals who had their first and brief exposure to malaria. Thirty-three individuals participated in the five crosssectional surveys, 15 with confirmed P. vivax infection while residing in the outbreak area (cases) and 18 who had not experienced malaria (non-cases). In the present study, we found that only 20% (three of 15) of the individuals who experienced their first P. vivax infection developed an antibody response to DBP; a secondary boosting can be achieved with a recurrent P. vivax infection. DNA sequences from primary/recurrent P. vivax samples identified a single dbp allele among the samples from the outbreak area. To investigate inhibitory antibodies to the ligand domain of the DBP (cysteine-rich region II, DBPII), we performed in vitro assays with mammalian cells expressing DBPII sequences which were homologous or not to those from the outbreak isolate. In non-immune individuals, the results of a 12-month follow-up period provided evidence that naturally acquired inhibitory antibodies to DBPII are short-lived and biased towards a specific allele.

Conserved and Variant Epitopes of Plasmodium vivax Duffy Binding Protein as Targets of Inhibitory Monoclonal Antibodies

“…Similar patterns of immune selection have been observed with other microbial adhesion molecules such as the influenza hemagglutinin (HA) (15,35). Therefore, consistent with this immune escape paradigm for microbial pathogen ligands is a concern that variation found in the DBPII may lead to strain-specific immunity, thereby reducing the effectiveness of any anti-DBP immune response (6,19,31).…”

The Plasmodium vivax Merozoite Surface Protein 1 Paralog Is a Novel Erythrocyte-Binding Ligand of P. vivax

“…Formation of tight junction and invasion of human erythro- cytes by P. vivax require the interaction of PvDBP with the Duffy antigen on the erythrocyte (4,40,41). Recent reports in Madagascar showed that genetically diverse isolates of P. vivax can cause both asymptomatic and symptomatic vivax malaria and show frequent transmission even in the Duffy-negative population (5, 6), suggesting that P. vivax, similar to P. knowlesi (42,43) and P. falciparum (3), can use an alternative pathway(s) to invade erythrocytes.…”

Antibody Responses and Avidity of Naturally Acquired Anti-Plasmodium vivax Duffy Binding Protein (PvDBP) Antibodies in Individuals from an Area with Unstable Malaria Transmission

“…Antibody responses to PvDBP have been shown in endemic populations of P. vivax infection in Papua New Guinea, [23][24][25] Brazil, [26][27][28] and Colombia. 29 In addition, different studies suggested that stronger humoral and cellular immune responses to PvDBP-II develop progressively with increasing age, 22,24,29,30 showing a boosting effect that was likely because of repeated exposures to the infection.…”